International Journal of Molecular Sciences Review An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps Oana Lelia Pop 1 , Dan Cristian Vodnar 1 , Zorita Diaconeasa 1 , Magdalena Istrati 2, 3 4 1, Adriana Bint, int, an , Vasile Virgil Bint, int, an , Ramona Suharoschi * and Rosita Gabbianelli 5,* 1 Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; [email protected] (O.L.P.); [email protected] (D.C.V.); [email protected] (Z.D.) 2 Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400158 Cluj-Napoca, Romania; [email protected] 3 1st Medical Clinic, Department of Gastroenterology, Emergency County Hospital, 400006 Cluj Napoca, Romania; [email protected] 4 1st Surgical Clinic, Department of Surgery, University of Medicine and Pharmacy Cluj Napoca, 400006 Cluj Napoca, Romania; [email protected] 5 Unit of Molecular Biology, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy * Correspondence: [email protected] (R.S.); [email protected] (R.G.) Received: 6 August 2020; Accepted: 2 October 2020; Published: 5 October 2020 Abstract: It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing gastrointestinal health. Adenomatous colon polyps have a high prevalence as colon cancer precursors, but in many cases, they are hard to diagnose in their early stages. Gut microbiota composition correlated with the presence of adenomatous colon polyps may be a noninvasive and efficient tool for diagnosis with a high impact on human wellbeing and favorable health care costs. This review is meant to analyze the gut microbiota correlated with the presence of adenomatous colon polyps as the first step for early diagnosis, prophylaxis, and treatment. Keywords: microbiota; adenomatous colon polyps; colon diseases 1. Introduction Trillions of microbes inhabit the human body, and most of them are present mainly in the gastrointestinal tract. They are more numerous than all of our cells [1]. By different mechanisms that are not fully understood, the microbiota balance influences our current and future wellbeing [2]. Because of their abundance in the gut, we can affirm that all gastrointestinal diseases are in direct correlation with the gastrointestinal microbiota balance. Early identification of any unusual changes in this balance can allow incipient diagnosis, which can ensure, in most cases, successful treatment and favorable long-term prognosis. A non-invasive, cost-effective, and efficient diagnosis can be ensured, but an intense study of the microbiota pattern in different intestinal diseases must be validated. The purpose of this review is to highlight the root of the mechanisms by which nutrients, food components, and medical interventions that spot the gut microbiota may play a role in the management of adenomatous colon polyps (ACPs). This paper will principally focus on the data relating to the effect of gut microbiota modulation and ACP prevention, amelioration, and treatment. Int. J. Mol. Sci. 2020, 21, 7359; doi:10.3390/ijms21197359 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, 7359 2 of 21 2. Human Microbiota and Colon Diseases The diversity and abundance of specific taxa (i.e., species, genus, family) in the gut microbiota plays a key role in the modulation of human health. Typically, the human gut microbiome is dominated by five main bacterial phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia. The thousands of metabolites produced by gut microbiota impact the host’s health significantly. Alterations in the gut microbiota and its metabolites due to a diet that is poor in fiber can lead to dysfunction of the gut’s epithelial barrier, production of pro-inflammatory cytokines (i.e., Interleukin 6 (IL6), Tumour Necrosis Factor alpha (TNF-α), Interleukin beta (IL1β)), and increase of the gut’s permeability [3,4]. A high-quality diet reflects gut microbiota diversity and richness [5]. Moreover, a maternal diet and weaning influence microbiota maturation [6]; that is, the infant’s flavor perception is modulated by the mother’s diet. From prenatal life and throughout development, children can learn to enjoy the flavors of healthy foods (i.e., vegetables) [7]. A fiber-rich diet (daily range of 28–35 g for adults) maintains the integrity of the mucus layer and barrier function of the gastrointestinal tract intact. In animal models, a chronic or intermittent fiber deficiency leads to dysbiosis with erosion of the mucus layer and barrier dysfunctions that cannot be prevented by adding purified prebiotic fibers (e.g., inulin, arabinoxylan, β-glucan) [8]. Dysbiosis due to the lack of fibers in our diet can increase the mucin-degrading bacteria population (e.g., B. fragilis, B. caccae, and A. muciniphila). Furthermore, dysbiosis can significantly decrease both the production of short chain fatty acids (SCFAs) and their protective anti-inflammatory properties [3,9]. An unhealthy diet containing red meat, processed meat, fat, sugar, and alcohol is associated with an increased risk of colorectal cancer (CRC), which is, in most of cases, derived from ACPs [10–15]. Animal-based diets significantly contribute to changes in microbiota composition, development of inflammation, DNA damage, and impaired apoptosis when compared with plant-based diets [16,17]. Microbiota metabolites formed from the oxidation of species in high-protein diets (i.e., polyamine and ammonia), high-fat diets (hydrogen sulphide from taurine, secondary bile acids), and alcohol (i.e., acetaldehyde) contribute to the generation of reactive oxygen species and genotoxicity in the host [3]. Bacteroides fragilis and Enterococcus faecalis release enterotoxins (i.e., fragylisin) and reactive oxygen species contributing to DNA damage, inflammation, and injury to the epithelial barrier. Changes in the abundance of specific bacteria have been used as a biomarker for the screening of gastrointestinal diseases including ACP, CRC, inflammatory bowel disease (IBD), and irritable bowel syndrome [18–20]. Gut microbiota dysbiosis has been observed in pouchitis, with an increase in Ruminococcus gnavus, Bacteroides vulgatus, and Clostridium perfringens, together with a lack of Lachnospiraceae genera (Blautia and Roseburia) [21]. Positive outcomes have been measured in adults with mild/moderate ulcerative colitis after 8 weeks of fecal microbiota transplantation (anaerobically prepared pooled stool) [22]. Enrichment of Fusobacterium nucleatum has been observed to induce immunosuppressive activity mediated by the inhibition of T cells in colorectal carcinogenesis [23]. A prospective cohort study on 1102 patients affected by colorectal carcinoma associates the amount of Fusobacterium nucleatum in colorectal cancer tissue with the tumor’s location [24]. Microbiota in colitis-associated cancer differs from that observed in subjects affected by sporadic cancer without IBD. Lower Firmicutes and Bacteroidetes with a significant increase in Proteobacteria was observed in colitis-associated cancer, while a reduction in Bacteriodes and an increase in Fusobacteria was identified in subjects affected by sporadic cancer [25]. Patients with Crohn’s disease and ulcerative colitis show a decreased bifidobacterial population and reduction in butyrate-producing bacteria, such as Faecalibacterium, Eubacterium, Roseburia, Lachnospiraceae, and Ruminococcaceae [26]. The microbial taxa Faecalibacterium, Bacteroides, and Romboutsia were depleted in adenomatous polyps and cancerogenic mucosa [27,28]. Furthermore, a higher abundance of bacteria belonging to the Campylobacter genus was identified in patients affected by CRC and adenomatous polyps when compared with healthy subjects [27]. Several taxa increased (i.e., Bilophila, Desulfovibrio, multiple Bacteroidetes species), while others decreased (i.e., Veillonella, Firmicutes, Clostridia, and Actinobacteria family Bifidobacteriales) in patients with adenomas living in the United States when compared with Int. J. Mol. Sci. 2020, 21, 7359 3 of 21 controls.Int. J. Mol. Sci. In 2020 addition,, 21, x FOR patients PEER REVIEW with dysbiosis demonstrated increased primary and secondary bile3 acidof 21 production and changes in sugar, protein, and lipid metabolism [29]. A graphic representation of the acid production and changes in sugar, protein, and lipid metabolism [29]. A graphic representation microbiota changes in subjects with ACP and CRC can be seen in Figure1. of the microbiota changes in subjects with ACP and CRC can be seen in Figure 1. Figure 1. Changes inin thethe gut gut microbiota microbiota composition composition in healthyin healthy colon, colon, adenoma adenoma colon, colon, and carcinoma and carcinoma colon. colon. 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